Susic D, Mandal A K, Jovovic D, Stojanov M, Djordjevic-Denic G, Kentera D
Institute for Medical Research, Belgrade, Yugoslavia.
J Clin Pharmacol. 1993 Apr;33(4):342-7. doi: 10.1002/j.1552-4604.1993.tb04667.x.
Chronic subcutaneous administration of heparin consistently lowers blood pressure in hypertensive rats. This antihypertensive effect is related at least in part to a concomitant decrease in hematocrit. Groups of spontaneously hypertensive (SHR) and normotensive Wistar (NWR) rats were treated with subcutaneous heparin (700 U/d) for 6 weeks. Weekly determinations of systolic blood pressure (tail-cuff) and hematocrit were done. Peripheral plasma renin activity, plasma aldosterone, plasma prostaglandins (PGs) (PGF2 alpha, PGI2), thromboxane A2, and urinary kallikrein were measured. Blood pressure responses of acute and chronic heparin treatment to vasoconstrictor substances, including angiotensin I, angiotensin II, and norepinephrine, were determined. As before, heparin produced a significant (P < .01) decrease in hematocrit in both SHRs and NWRs, but a parallel decrease in blood pressure was noted only in SHRs. A significant (P < .001) increase in plasma renin activity was found in heparin-treated SHRs and NWRs; however, a corresponding elevation of plasma aldosterone level was noted only in heparin-treated NWR. Plasma aldosterone level significantly (P < .01) decreased in heparin-treated SHRs. Plasma PGs and urinary kallikrein levels were not different among the groups. The blood pressure responses to vasoconstrictor substances were essentially similar among the heparin-treated and control groups. These findings suggest that PGs or kallikrein have a slight or no role in determining the antihypertensive effect of heparin. Conversely, the results suggest that a reduced aldosterone level contributes to the antihypertensive mechanism of heparin.
长期皮下注射肝素可使高血压大鼠的血压持续降低。这种降压作用至少部分与同时出现的血细胞比容降低有关。将自发性高血压（SHR）大鼠和正常血压的Wistar（NWR）大鼠分为几组，皮下注射肝素（700 U/天），持续6周。每周测定收缩压（尾套法）和血细胞比容。检测外周血浆肾素活性、血浆醛固酮、血浆前列腺素（PGs）（PGF2α、PGI2）、血栓素A2和尿激肽释放酶。测定急性和慢性肝素治疗对血管收缩物质（包括血管紧张素I、血管紧张素II和去甲肾上腺素）的血压反应。如前所述，肝素使SHR和NWR的血细胞比容均显著降低（P <.01），但仅在SHR中观察到血压平行降低。在肝素治疗的SHR和NWR中发现血浆肾素活性显著升高（P <.001）；然而，仅在肝素治疗的NWR中观察到血浆醛固酮水平相应升高。肝素治疗的SHR中血浆醛固酮水平显著降低（P <.01）。各组之间血浆PGs和尿激肽释放酶水平无差异。肝素治疗组和对照组对血管收缩物质的血压反应基本相似。这些发现表明，PGs或激肽释放酶在决定肝素的降压作用中作用轻微或无作用。相反，结果表明醛固酮水平降低有助于肝素的降压机制。
